Biomedical subjects

J Fujimoto

Publications and source records attributed to J Fujimoto.

At least 163 records · Page 9Linked to original sources

PubMed1997

Expression of hepatocyte growth factor and its receptor, the c-met proto-oncogene, in hepatocellular carcinoma.

The c-met proto-oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a potent mitogen and motogen for epithelial cells. Because of its profound effects on cell growth and motility, HGF may be important in the development of cancer metastases in hepatocellular carcinoma (HCC). In this study, we examined HGF concentration and expression of the c-met proto-oncogene product (c-Met) in 62 patients with HCC to determine the relationship between the level of expression and clinicopathological features, and patient outcome following hepatectomy. Western blotting was used to examine the c-Met expression, and HGF concentration in tumors was measured using an enzyme-linked immunosorbent assay. c-Met was found to be overexpressed in HCC compared with nontumorous liver tissue (P < .01), and correlated with an increased incidence of intrahepatic metastases (P = .039). Patients were divided into two groups: low c-Met HCC and high c-Met HCC. Patients with high c-Met HCC had a significantly shorter 5-year survival than patients with low c-Met HCC (33.5% vs. 80.3%, respectively; P < .05). However, there was no correlation between HGF concentration in the tumor tissue and clinicopathological factors and patient survival. These results indicate that the expression of c-Met played an important role in tumor growth and metastases in patients who underwent hepatectomy for HCC.

Adult↗

PubMed1997

Expression of hepatocyte growth factor and its receptor c-met proto-oncogene in hepatocellular carcinoma.

The c-met proto-oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a potent mitogen and motogen for epithelial cells. Because of its profound effects on cell growth and motility, HGF may be important in the development of cancer metastases in hepatocellular carcinoma (HCC). In this study, we examined HGF concentration and expression of the c-met-proto-oncogene product (c-met) in 62 patients with HCC to determine the relationship between the level of expression and clinicopathological features, and patient outcome following hepatectomy. Western blotting was used to examine the c-met expression, and HGF concentration in tumors was measured using an enzyme-linked immunosorbent assay. c-met was found to be overexpressed in HCC compared with nontumorous liver tissue (P < .01), and correlated with an increased incidence of intrahepatic metastases (P = .039). Patients were divided into two groups, low c-met HCC and high c-met HCC. Patients with high c-met HCC had a significantly shorter 5-year survival than patients with low c-met HCC (33.5% vs. 80.3%, respectively; P < .05). However, there was no correlation between HGF concentration in the tumor tissue and clinicopathological factors and patient survival. These results indicate that expression of c-met played an important role in tumor growth and metastases in patients who underwent hepatectomy for HCC.

Adult↗

PubMed1997

Cellular DNA content and histopathological analysis in hepatocellular carcinoma with multiple nodules.

Multiple tumors within the liver are a characteristic feature of hepatocellular carcinoma (HCC). This study investigated alterations in the histologic type and DNA content of multiple nodules of HCC. Both a pathologic examination and flow cytometric DNA analysis were performed on 49 resected specimens of multinodular HCC. The results showed that 35 cases had multiple metastatic satellite nodules around the main tumor (group 1), while 14 had two solitary nodules in different segments without satellite nodules (group 2). In group 1, 28 out of 35 (80.0%) showed a single DNA index while 7 (20.0%) revealed two different DNA contents in the main tumor. The histological type, cytological grade, and DNA index were equivalent between the main and satellite tumors in 100%, 88.6%, and 97.1% of the cases, respectively. In group 2, all tumors showed a single histological type, cytological grade, and DNA index in each nodule. The histological type was identical in 85.7% of the pairs of nodules, but the cytological grade and DNA index were different in 42.9% and 85.7%, respectively. The patients in group 2 showed a significantly higher 5-year survival rate than that in group I (64.8% vs 27.2%, P < 0.05). This study thus indicates that the cytological grade and DNA content are useful in distinguishing multicentric occurrence from intrahepatic metastasis in HCC.

Adult↗

PubMed1997

Comparison between transabdominal-vulvar and transvulvar approaches for peritoneal vaginoplasty in patients with congenital absence of the vagina.

To compare the operative and sexual efficiencies of transabdominal-vulvar and transvulvar techniques for peritoneal vaginoplasty in patients with congenital absence of the vagina, we treated 36 patients by peritoneal vaginoplasty, originally described by Rothman, 31 with the transabdominal-vulvar technique and five with a new transvulvar technique. Both techniques equally gave the patients excellent sexual conditions. The mean blood loss was the mean duration of operation were 278 +/- 268 g and 1 degree 54' +/- 48' in the transabdominal-vulvar technique and 50 +/- 52 g and 58' +/- 11' in the transvulvar technique. The latter was significantly less than the former. Therefore, the transvulvar technique for peritoneal vaginoplasty in patients with congenital absence of the vagina was thought to be better than the transabdominal-vulvar technique.

Adolescent↗

PubMed1997

Antiestrogenic compounds inhibit estrogen-induced expressions of basic fibroblast growth factor and its mRNA in well-differentiated endometrial cancer cells.

1. The levels of basic fibroblast growth factor (FGF) expression and secretion and its messenger ribonucleic acid (mRNA) expression in well-differentiated endometrial cancer (Ishikawa) cells were significantly increased by estradiol. 2. This increase was significantly inhibited by tamoxifen, progestins (progesterone, medroxyprogesterone acetate [MPA], and 17 alpha-hydroxyprogesterone), and to some extent danazol, but not by terahydrocortisol and hydrocortisone. 3. Estrogen might stimulate the basic FGF secretion of endometrial cancer cells, at least for neovascularization, and antiestrogenic compounds may inhibit the estrogen-induced event.

Adenocarcinoma↗

PubMed1997

Expression of estrogen receptor exon 5 splicing variant (ER E5SV) mRNA in gynaecological cancers.

Estrogen receptor exon 5 splicing variant (ER E5SV) mRNA has been found in tumours and the corresponding normal tissues, being transcriptionally active without ligand binding. Therefore, the expression of ER E5SV mRNA in gynaecological cancers was studied. The presence of ER E5SV mRNA was demonstrated in the normal ovary, uterine endometrium and cervix and their corresponding cancers. The ratio of ER E5SV/ER WT mRNA expression increased in some cases of metastatic tumour, but did not decrease in any case. Relative overexpression of ER E5SV mRNA might contribute to dominant positive properties and metastatic potential. Therefore, detection of ER E5SV mRNA abundance might be a useful indicator of metastatic potency in gynaecological cancers.

Adult↗

PubMed1997

Effects of danazol and progesterone on sex hormone-binding globulin mRNA expression in human endometrial cancer cell line Ishikawa.

To ascertain one of the biological effects of danazol and progesterone on the uterine endometrial cancer cell line, Ishikawa, we investigated the effects of these steroids on sex hormone-binding globulin (SHBG) mRNA expression by competitive reverse transcription-polymerase chain reaction-Southern blot analysis (RT-PCR-SBA). Estradiol-17beta (E2) in any concentration given did not exert any significant effect on the expression of SHBG mRNA. Danazol and progesterone significantly (P < 0.05) suppressed the expression of SHBG mRNA dose-dependently starting at a concentration of 10(-6) and 10(-8) M, respectively. Progesterone, in a low concentration (10[-10] M) with E2 (10[-8] M), significantly (P < 0.05) increased the expression of SHBG mRNA, but danazol did not. In contrast, danazol and progesterone in high concentrations (10[-6] to 10[-5] M) with E2 (10[-8] M) significantly (P < 0.05) suppressed its expression. The time course study showed the time-dependent decrease of SHBG mRNA level by danazol and progesterone (10[-6] M) with or without E2 (10[-8] M), except for a temporal increase by progesterone. These findings suggest that danazol and progesterone in a superphysiological milieu down-regulate the intracellular SHBG-related steroidal actions, and that progesterone in a physiological milieu with estrogen up-regulates it in a hormone-dependent cell line. A decrease of intracellular SHBG caused by high-dose danazol or progesterone might partly contribute to the abolition of the intracellular estrogen-dominant milieu, and be related to the inhibition of estrogen-dependent growth of some endometrial cancer cells.

Adenocarcinoma↗

PubMed1997

Expression of sex hormone-binding globulin exon VII splicing variant mRNA in human uterine endometrium.

We have demonstrated the expression of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA in human uterine endometrium, using the reverse transcription-polymerase chain reaction-Southern blot and DNA sequencing analyses. Analysis of the missing base pairs corresponded to the entire exon VII, which are considered to encode a portion of the steroid-binding site. Therefore, the steroid-binding affinity of this variant might be different from that of the SHBG wild type. In uterine endometria, the wild-type and variant mRNA levels tended to increase with the advance of the menstrual phase, but the ratio of the SHBG variant mRNA to SHBG wild-type mRNA levels showed no significant difference during the menstrual cycle. So far, there are no indications that the SHBG variant has any biological or clinical implications in human uterine endometrium.

Adult↗

PubMed1997

Clinical implication of expression of progesterone receptor form A and B mRNAs in secondary spreading of gynecologic cancers.

This study was designed to determine the clinical implication of expression of progesterone receptor form A (PR-A) and B (PR-B) mRNAs in secondary spreading of gynecologic cancers. Approximately equal expression of PR-A and PR-B mRNAs was designated as type AB and dominant expression of PR-B mRNA as type B. Alteration from type AB to type B in the metastatic cancers occurred in 3/8 cases of uterine endometrial cancers, 2/8 cases of uterine cervical cancers, and 2/8 cases of ovarian cancers. Other cancers revealed type B regardless of primary or metastatic status. Thus, all metastatic cancers studied revealed type B. These results suggest that transcription of PR-A mRNA may be damaged, which might lead to uncontrolled overexpression of PR-B mRNA in metastatic lesion, and that the type B status could reveal a highly malignant phenotype in these three gynecologic cancers.

Adult↗

PubMed1997

Synthesis and cleavage of oligodeoxynucleotides containing a 5-hydroxyuracil residue at a defined site.

Oxidation and hydrolysis of a cytosine residue can lead to the formation of 5-hydroxyuracil in DNA. The biological consequences of this modification are not fully understood. To facilitate biochemical and biophysical studies aimed at elucidating the effects of this modification in DNA, we have developed a solid-phase synthetic method for the placement of 5-hydroxyuracil residues at defined sites in oligodeoxynucleotides. This method is based upon the enhanced acidity of the 5-hydroxyl proton which allows selective aqueous acetylation. Under standard aqueous ammonia deprotection conditions, however, we observed that 5-hydroxyuracil residues are lost substantially from synthetic oligonucleotides. Substitution of aqueous ammonia with methanolic potassium carbonate and the use of phosphoramidite derivatives with alternatively protected amino groups allow synthesis of oligonucleotides containing 5-hydroxyuracil and all normal bases in high yield. The composition of the oligodeoxynucleotides prepared by this method has been verified by enzymatic digestion followed by high-performance liquid chromatography (HPLC) analysis as well as acid hydrolysis followed by GC/MS analysis. The location of the 5-hydroxyuracil residue is demonstrated by selective permanganate oxidation of the 5-hydroxyuracil residue followed by beta-elimination. We have also probed a synthetic oligonucleotide containing a unique 5-hydroxyuracil residue with uracil DNA N-glycosylase, previously reported to remove this lesion from DNA.

Antineoplastic Agents↗

PubMed1997

Frequent detection of hepatitis B virus X-gene DNA in hepatocellular carcinoma and adjacent liver tissue in hepatitis B surface antigen-negative patients.

Hepatitis B virus is associated with human hepatocellular carcinoma. We performed polymerase chain reaction for the X, C, S, and preS2/S regions of the viral genome in 23 hepatitis B surface antigen-negative hepatocellular carcinomas and adjacent liver. Hepatitis B viral genomes were detected in 17 of 23 tumors and adjacent tissues (73.9%). Among recognized transactivators, the X gene was present in 16 (69.6%) cases of hepatocellular carcinoma, but preS2/S was detected in only 7 (30.4%). Hepatitis B virus C and S regions were detected in 3 (13.0%) and 9 (39.1%) hepatocellular carcinomas, respectively. Serologic study revealed antibodies to hepatitis B surface antigen, hepatitis B core antigen, and hepatitis B e antigen in 14 patients; among these, X-gene DNA was detected in 12 of 14 tumors (85.7%). The X gene was also detected in 4 of 9 tumors of seronegative patients. The X gene, present in many hepatocellular carcinomas, may promote hepatocellular carcinoma in hepatitis B surface antigen-negative patients.

Adult↗

PubMed1997

Congenital leukaemia with a mixed phenotype of megakaryoblasts and erythroblasts: a case report and characterization of the blasts.

We present a congenital leukaemia with a mixed phenotype of megakaryoblasts and erythroblasts. A newborn male with exopthalmus and multiple skin nodules, had bone marrow blasts which expressed CD41b, CD42b, glycophorin-A and haemoglobin, but monocyte or lymphoid markers were negative. The patient achieved a complete remission with chemotherapy. Blasts cultured for a few months expressed erythroid markers but lost the megakaryocytic phenotype, although addition of phorbol ester induced the latter phenotype. Spontaneous colony formation was observed in semi-solid culture and the number of colonies was increased by erythropoietin. Detailed studies further indicated the heterogeneity of congenital leukaemia.

Erythroblasts↗

PubMed1997

Expression of sex hormone-binding globulin and corticosteroid-binding globulin mRNAs in corpus luteum of human subjects.

To understand the biology of sex steroids in human ovarian corpus luteum, the expression of intracellular sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) mRNAs as a manifestation of intracellular SHBG and CBG expression was determined. The expression of SHBG and CBG mRNAs was detected in all samples analyzed. Luteal SHBG mRNA level showed no significant change during the endometrial secretory phase of the menstrual cycle. On the other hand, luteal CBG mRNA level was significantly higher (p < 0.05) at the mid-secretory phase than that at the early and late secretory phases of the endometrium. These findings suggest that human ovarian corpus luteum synthesizes SHBG and CBG intracellularly, CBG being plausibly involved in the functional life span of corpus luteum.

Adult↗

PubMed1997

Expression of sex hormone-binding globulin mRNA in uterine cervical cancers.

To explore the role of sex hormone-binding globulin (SHBG) in the intracellular steroidal actions in human uterine cervical cancers, the expression of SHBG mRNA as a manifestation of intracellular SHBG expression was investigated using the competitive reverse transcription-polymerase chain reaction-Southern blot analysis. The expression of SHBG mRNA was detected in all cervical endometria and cancers analyzed. The levels of SHBG mRNA in cervical cancers were significantly lower (p < 0.01) than in the normal cervical endometrium. In cervical cancers, the levels of SHBG mRNA in cervical adenocarcinomas were significantly higher (p < 0.01) than in keratinizing and small cell nonkeratinizing squamous cell carcinomas, and tended to be higher than in large cell nonkeratinizing squamous cell carcinomas. There was no difference in expression among the clinical stages of cervical cancers. These data suggest that human uterine cervical cancers, especially adenocarcinomas, might synthesize SHBG intracellularly, and might conserve the activity of SHBG-related steroidal mechanisms to some extent.

Adult↗

PubMed1997

Comparative study on expression of plasminogen activator inhibitor 1 and its mRNA in endometrial cancers and normal endometria.

The effects of the endocrine milieu on growth, invasion and metastasis, associated with neovascularization of endometrial cancer, the expression of plasminogen activator inhibitor 1 (PAI-1), and its mRNA in endometrial atypical hyperplasia and cancer, and normal endometria as controls were determined in premenopausal and postmenopausal women. In premenopausal women, the levels of PAI-1 and its mRNA in normal endometria were significantly higher than in endometrial atypical hyperplasia and cancer. On the other hand, in postmenopausal women, the results were reversed. There was no difference in the expression of PAI-1 and its mRNA in the various histological grades and clinical stages in endometrial cancers, while the expression of PAI-1 in other cancers increased during tumor progression. In our previous study, the expression of PAI-1 and its mRNA in well-differentiated endometrial cancer cell lines was dependent upon estrogen and progesterone. This might be partially related to the endocrine milieu, especially in endometrial atypical hyperplasia and well-differentiated endometrial cancer, which seems to be dependent on sex steroids. Therefore, endometrial cancer of any histological grade and clinical stage might maintain PAI-1 expression in both premenopausal and postmenopausal women, which may modulate, at least in part, growth, invasion and metastasis associated with neovascularization of endometrial cancer.

Adult↗

PubMed1997

Expression of E-cadherin and alpha- and beta-catenin mRNAs in uterine cervical cancers.

To show the mRNA expressions of E-cadherin and alpha- and beta-catenin-which mainly compose the adherens junction-associated with invasion and metastasis of uterine cervical cancers, we studied the expression of E-cadherin and alpha- and beta-catenin mRNAs in cancers in comparison with normal counterparts. The integral expression of E-cadherin and alpha- and beta-catenin mRNAs was suppressed in the metastatic lesions of advanced uterine cervical cancers, while it was not in the primary tumors. Therefore, the suppressed expression of main adhesion molecules in the adherens junction might contribute to adherens-junctional dysfunction, which might lead to invasiveness and metastatic potential of advanced uterine cervical cancers as one rate-limiting step.

Adult↗

PubMed1997

Ovarian steroids regulate the expression of basic fibroblast growth factor and its mRNA in fibroblasts derived from uterine endometrium.

The role of stromal cells in basic fibroblast growth factor (FGF) supply for endometrial neovascularization during the menstrual cycle was investigated. The concentrations of intracellular and secreted FGF, and FGF mRNA expression were determined in fibroblasts derived from uterine endometrium as a substitute for stromal cells. The influence of sex steroids on protein and mRNA expression was investigated. The concentration of FGF and its mRNA expression in the fibroblasts was significantly increased by oestradiol, and these increased concentrations were diminished by progesterone. It is suggested that oestrogen stimulates FGF secretion from the stromal cells, an effect which is inhibited by progesterone. Therefore, endometrial neovascularization might be partially regulated by stromal-derived FGF under the influence of sex steroids, through a paracrine cell-to-cell interaction.

Adult↗

PubMed1997

Localization of sex hormone-binding globulin mRNA expression in human uterine endometrium.

To identify the dominant cell of sex hormone-binding globulin (SHBG) synthesis in human uterine endometrium, we investigated the expression of endometrial SHBG mRNA using Northern blot and in situ hybridization analyses. Expression of a single dominant SHBG mRNA was detected in uterine endometrium using Northern blot analysis. Additionally, SHBG mRNA expression was demonstrated by in situ hybridization in the glandular epithelial cells of the endometrium, but not in the stromal cells. Therefore, in the endometrial glandular epithelial cells, SHBG might be involved in the intracellular steroidal action, but not in the endometrial stromal cells. The SHBG-mediated effects on the endometrium appear to be heterogeneous.

Adult↗